In vertebrates, the hypothalamus and pituitary have well-defined roles in the control of reproduction. Gonadotropin-releasing hormone (“GnRH”) is the central regulatory neurohormone controlling reproduction in all vertebrates. GnRH is a ten amino-acid peptide, synthesized in the hypothalamus, and released into the hypophysial portal blood system, directly into the pituitary gland as in the case of teleost fish, or by diffusion as in the case of Agnathans. Upon response to external cues (such as environmental cues like water temperature) and internal cues, GnRH is released and acts at the pituitary gland to stimulate the synthesis and release of the gonadotropins, which then travel by systemic circulation to the gonads, thereby regulating steroidogenesis and gametogenesis.
GnRH action at the pituitary is mediated by specific, high-affinity receptors; these GnRH receptors are 7-transmembrane-domain (7-TM) G protein-coupled receptors (GPCRs). 7-TM GPCRs are one of the most abundant families of proteins in the human genome, and they mediate a large portion of the cellular signals necessary for life. The GnRH receptors are the only subgroup within this protein family in which certain members lack an important structural feature: the intracellular, C-terminal tail. Many studies have demonstrated the importance of this intracellular domain for proper activity and regulation of receptors, and within the GnRH family this structural variance is thought to be one of the central features contributing to GnRH signal integration and gonadotropin control.